The medicinal chemistry of selected halogenated diketopiperazines CYCLO(CIS-PRO-4F-PRO) and CYCLO(L-PHE-4I-VAL)

Generally, peptides are selective and efficacious compounds; as a result, they are the best candidates for drug discovery and development. Most peptide-based drugs have been approved for clinical use. The 2,5-Diketopiperazines (DKPs), also known as cyclic dipeptides, are simple compounds which come from nature. Many DKPs are extracted from animals and plants. For example, cyclo(Proline(Pro)-Leucine(Leu)), cyclo(Proline-Valine(Val)), cyclo(Proline-Phenylalanine(Phe)) etc. In this study cyclo(cis-Proline(Pro)-4F-Proline(Pro)) and cyclo(L- Phenylalanine(Phe)-4I- Valine (Val)) were synthesized from their linear esters using a method modified by Milne et al. (1992). This method yielded good results. However, cyclo(L-Phe-4I-Val) degraded due to physicochemical stability attributes caused by hygroscopicity and photosensitivity. Quantitative analysis and evaluation of physicochemical properties of each dipeptide was achieved by using scanning electron microscopy, thermal analysis (differential scanning calorimetry and thermogravimetric analysis) and X-ray powder diffraction. To determine the purity of the cyclic dipeptide, high performance liquid chromatography and thin layer chromatography was used. The structural elucidation of the cyclic dipeptides was carried by employing infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy and, molecular modelling and computational chemistry. The aim of this research was to discover possible biological activity of cyclo(cis-Pro-4-F-Pro) and cyclo(L-Phe-4I-Val) with respect to their antimicrobial, anticancer, anti-diabetic and haematological effects. Cyclo(cis-Pro-4Fluoro-Pro) had no inhibitory effect on the antimicrobial strains tested, and cyclo(L-Phe-4Iodo-Val) could not be tested as the compound decomposed